The delivery of therapeutics to the lung for the local treatment of pulmonary disorders (asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis) has long been utilized, and inhalation therapy for the treatment of systemic diseases (e.g. diabetes) has been the focus of increasing academic and industry research within the past decade. Given its extremely large surface area, mild environment, and ease of administration, in contrast to oral and intravenous routes of drug delivery, the lung presents an especially attractive avenue of therapeutic delivery.
However, pulmonary drug delivery is not without its obstacles. For drug particles to deposit in the deep lung, where they exert their therapeutic action, they must possess certain physical properties. Specifically, the drug particles must have an aerodynamic diameter below 5 microns, where the aerodynamic diameter encompasses both the density and geometric diameter of the drug particle. Accordingly, aerosolized drug particles must be less than 5 microns in aerodynamic diameter when they exit an inhaler to deposit in the deep lung.
While both liquid (metered dose inhalers, nebulizers) and solid (dry powder inhalers) dosage forms are used for inhalation therapy, dry powder drug formulations are garnering an increasing share of the market due to their dose flexibility and excellent drug stability. While dry powder formulations offer many advantages over liquid formulations, their performance is plagued by low drug delivery (generally below 30% of the total dose is delivered to the deep lung) and high throat and upper airway deposition. This is evidence that the majority of the drug particles exiting the inhaler are not in the primary particle size (<5 microns), but rather in agglomerates or still attached to carrier particles, which due to their large aerodynamic diameter deposit in the throat and upper airways.
However, due to the micron dimensions of the drug particles, the cohesive forces that exist between them, due primarily to Van der Waals and electrostatic forces, are quite strong and prevent drug particles from being readily deaggregated as they exit the inhaler. Even while the primary particle size (i.e., the size of a single particle of the drug powder) may be below 5 microns in diameter, a large fraction of the dose may comprise agglomerated drug particles many times the size of the primary particles, leading to drug deposition in the mouth, throat, or upper airways (possibly producing toxic side effects) and/or drug deposition in the inhaler (reducing efficiency of the dose).
Drug particle agglomeration may occur before and/or during a coating process. Regardless, one potential problem with dry coating of surfaces (e.g., a film, carrier particle surfaces, or other substrates used in dry powder inhalers) with microparticles of a drug is that drug-drug cohesive interactions are not effectively eliminated. Another possible problem is that press-on forces between the drug microparticles and the surface can be large enough to prevent the detachment of the drug particles from the surface during inhalation.
Thus, the dry coating of surfaces with microparticles is a crucial step in developing an effective dry powder drug delivery platform, as well as in a number of different applications. Research has shown that there is an optimum range for press-on forces during coating; strong enough to adhere the drug to the film surface, yet sufficiently weak so that the drug is readily dispersed during aerosolization. To this end, it may be desirable to provide apparatuses for coating and coating methods capable of modulating the press-on forces between drug and surface during coating.
It may be desirable to provide apparatuses and methods for dosing and coating inhalation powders onto surfaces that deaggregate drug powder into particles of primary size and reduce the presence and subsequent dispersion of drug agglomerates that could undesirably deposit in the mouth and upper airways. It may also be desirable to provide apparatuses and methods for coating surfaces with drug microparticles sized to be deposited in the deep lung, thereby improving the efficacy of current dry powder inhalers.